scholarly journals Flow Cytometry-Assessed PD1/PDL1 Status in Tumor-Infiltrating Lymphocytes: A Link With the Prognosis of Diffuse Large B-Cell Lymphoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Zihang Chen ◽  
Xueqin Deng ◽  
Yunxia Ye ◽  
Wenyan Zhang ◽  
Weiping Liu ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
Tumor Infiltrating Lymphocytes ◽  
B Cell Lymphoma ◽  
Healthy Controls ◽  
Tissue Samples ◽  
Large B Cell Lymphoma ◽  
Infiltrating Lymphocytes

The PD1/PDL1 status of tumor-infiltrating lymphocytes (TILs) in diffuse large B-cell lymphoma (DLBCL) reflects immune function. However, the previously reported methods for evaluating this status are complex and may not be widely used in clinical practice. In addition, these studies did not introduce healthy controls to designate the cut-off when evaluating the prognostic value of the status. In this study, we retrospectively evaluated the PD1/PDL1 status in TILs of 24 DLBCL tissue samples and normal immune cells in 61 demographically matched healthy controls (tissue samples from patients with reactive hyperplasia [RH]) by flow cytometry. We investigated the prognostic value of the PD1/PDL1 status in TILs by precisely determining the cut-off value and assessing the reliability of flow cytometry. The mean fluorescence intensity (MFI) of PD1 in TIL-T-cells (TIL-Ts; median, 110) and CD8+TIL-Ts (median, 64) was significantly higher than that of CD3+T-cells (median, 64) and CD8+ T-cells (median, 34) in RH. The cut-off values of PD1/PDL1 status for analyzing prognostic values were defined considering the PD1/PDL1 status of samples from both patients with DLBCL and healthy controls. High MFI of PD1 in TIL-Ts (MFI >108, P = 0.022), high proportion of PD1+CD4+TIL-Ts (>1.1% of CD4+TIL-Ts, P = 0.049), high proportion of PD1+CD8+TIL-Ts (>2% of CD8+TIL-Ts, P = 0.025), and high MFI of PDL1 in TIL-Ts (MFI >83, P = 0.023) were risk factors for inferior prognosis of DLBCL. Our results indicate that flow cytometry is a reliable and convenient method for evaluating the immune-checkpoint status of TILs, which probably holds major implications in clinical practice.

Peripheral Blood Lymphocytic Profile in Patients with Diffuse Large B Cell Lymphoma and Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4656-4656
Author(s):  
Fernando Cavallin ◽  
Giovanni Vicario ◽  
Paolo Manente ◽  
Rosa Di Gaetano ◽  
Giuseppe Tagariello
Keyword(s):  
Flow Cytometry ◽  
T Cells ◽  
B Cell ◽  
Peripheral Blood ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Peripheral Blood Lymphocytes ◽  
Over Expression ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) are the most common adult low-grade non Hodgkin’s lymphomas. The influence of these diseases in peripheral blood lymphocytes is not well defined. Indeed the lymphocytic arrangement can be altered on account of the leukaemic form (although it slightly ever occurs); on the other hand the cause of occasional anomalies can be the involvement of the immune system against neoplasm. In order to contribute to the knowledge of these conditions we have analysed, at diagnosis, the lymphocytic immunophenotype in peripheral blood of 61 subjects: 27 were affected by DLBCL, average age 68, and 34 by FL, average age 61 years. Therefore we quantified the number of lymphocytes and evaluated essential markers, using flow cytometry, to define T, B, NK subsets by: CD3, CD4, CD8, CD19, SIgk, Sigl, CD56, and expression of CD11a molecule on T CD8. The absolute peripheral blood lymphocytes count presented a reduction in 51% and in 32% of the cases with an increase in 4% and in 3% of the subjects respectively considering DLBCL and FL. On the contrary T cells (CD3) had similar decrease, 33% and 32%, and different augmentation 15% and 3%. T cells ratio CD4/CD8 was under normal in 23% and in 12% of the patients but over normal in 12% and 29% always in DLBCL and FL. B cells (CD19) were reduced in 35% and in 12% of the subjects but increased in 8% and in 14%, whereas clonal restriction was present in 8% and in 20% of the components of the two groups. Natural Killer lymphocytes (CD56) were under normal in 12% and in 6% of bthe cases but over in 40% and 20%. Finally CD11a was over-expressed in 87% and in 68% of the patients of the respective pathologies. After selecting patients aged over 60 years, following four parameters that showed a significant variability was obtained: 1) lymphopenia in 50% of the cases in both groups; 2) similar results 11% and 15% about clonal restriction; 3) increase of the NK population 42% and 30% in DLBCL and FL; 4) very high over-expression of CD11a on T CD8 of 90% and 80%. Therefore DLBCL and FL are lymphoproliferative diseases where there is an important subtraction of lymphocytes, particularly in elderly people, from peripheral blood (perhaps because of accumulation in lymphnodes). These lesions present clonal restriction of B cells only in few cases (confirming the low known leukaemic form) while Natural Killer population are well represented especially in DLBCL. The over-expression of CD11a is the most altered parameter and seems almost a typical marker of these diseases above all in over 60 years subjects. Consequently if rarely happens that a leukaemic form of DLBCL and FL are found by flow cytometry however immunological defined alterations are very frequent in most of the cases of old patients.

scholarly journals LAG3 and PD1 Regulate CD8+ T Cell in Diffuse Large B-cell Lymphoma Patients

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Ying Liu ◽  
Xinhong Guo ◽  
Lingbo Zhan ◽  
Lei Wang ◽  
Xinyou Wang ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Cd8 T Cells ◽  
Cd4 T Cells ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Immune Checkpoints ◽  
Healthy Controls ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Background. Diffuse large B-cell lymphoma (DLBCL) is a clinically and genetically heterogeneous lymphoid malignancy. The unsatisfactory outcome for refractory patients has prompted efforts to explore new therapeutic approaches for DLBCL. However, the mechanisms involved in treatment associated with immune checkpoints remain unclear. This study is aimed at investigating the potential roles of programmed cell death protein 1 (PD1) and lymphocyte activation gene 3 (LAG3) in CD8+ T cells for treatment in DLBCL. Methods. Utilizing flow cytometry, we examined the content of T cells, the levels of cytokines, and the expression of PD1 and LAG3 in patients with DLBCL as well as in healthy controls. Levels of cytokines in CD8+ T cells from DLBCL patients before and after treatment were compared by blocking of PD1 and LAG3 in magnetic bead-sorted CD8+ T cells. Results. We found that the proportion of CD4+ T cells and CD8+ T cells was increased in DLBCL patients after treatment. The levels of cytokines trended toward those of healthy controls in treatment. PD1 (+), LAG3 (+), or PD1 (+) LAG3 (+) were all expressed in lower amounts in CD4+ T cells and CD8+ T cells after treatment than in untreated DLBCL patients. In addition, blockade of PD1 and LAG3 in sorted CD8+ T cells markedly inhibited cytokine production in response to treatment. Conclusion. PD1 and LAG3 in CD8+ T cells may be important targets of therapy and play therapeutic role in patients with DLBCL.

Prognostic value of PD-1 and TIM-3 on CD3+ T cells from diffuse large B-cell lymphoma

2015 ◽  
Vol 75 ◽  
pp. 83-87 ◽  
Author(s):  
Li Zhang ◽  
Hui Du ◽  
Tai-wu Xiao ◽  
Ji-zhu Liu ◽  
Guo-zhen Liu ◽  
...  
Keyword(s):  
T Cells ◽  
B Cell ◽  
Prognostic Value ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell
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